It is the purpose of the proposed studies to define some of the cellular mechanisms regulating cerebrovascular tone. Due to the problems inherent in voltage clamping a syncytial tissue such as vascular smooth muscle, we will use alternative methods to determine the extent to which membrane electrical events control force development in cerebral arterial muscle. Membrane potential (Em), action potential characteristics and electrogenic ion transport potentials will be recorded from smooth muscle cells within isolated cat cerebral arteries with intracellular microelectrodes. Mechanical events will be recorded with highly sensitive, specially fabricated myographs. The ionic species contributing to the inward current of the arterial muscle action potential (with special reference to Ca++) and the existence of a Na+/Ca+ exchange process will be determined by ion substitution experiments. Measuring the maximal rate of rise of the action potential as the muscle membrane is depolarized will determine the relationship between Em and channels carrying inward current. Similarly, the relationship between Em and tension will be determined by simultaneous recording of electrical and mechanical events. The cellular mechanisms underlying myogenic behavior will be examined in resistance vessels by optically measuring diameter, while recording the Em in response to increasing transmural pressure. The changes in the above parameters in response to elevated PCO2, serotonin, norepinephrine, ouabain and Ca++ channel blockers will be determined. Special attention will be focused on determining the mechanism of cerebral vasospasm, following subarachnoid hemorrhage by measuring electrical, mechanical, and myogenic responses to blood and platelet rich serum applied to the adventitial side of cerebral arteries. The proposed studies will yield information regarding: (1) the membrane contribution to force development in cerebral vascular muscle; (2) the cellular mechanisms underlying stretch activation (myogenic behavior) in cerebral arteries; and (3) the alteration of these parameters which occurs when blood is in contact with the adventitia of cerebral arteries in an effort to determine some of the pathophysiology associated with subarachnoid hemorrhage.